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Nakajo Nishimura syndrome



Other Names:
Amyotrophy fat tissue anomaly
Categories:

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 2615

Definition
Nakajo-Nishimura syndrome (NNS) is a rare autoinflammatory disorder belonging to the proteasome disability syndrome (see this term) group, and characterized by pernio-like lesions appearing in infancy followed by recurrent fever, nodular skin eruption, partial lipodystrophy (mainly in upper extremities and face) and joint contractures.

Epidemiology
The prevalence is unknown. In Japan, 30 cases have been identified to date.

Clinical description
Onset appears in early infancy with pernio-like lesions (mainly on fingertips and earlobes) that usually appear during the first winter after birth. This is followed by periodic fever and nodular erythema with infiltration and induration. Progressive lipomuscular atrophy (mainly in the upper body) and interphalangeal joint contractures lead to the characteristic thin and angular facial appearance and to the long clubbed fingers seen eventually in all patients. Central obesity and myositis, leading to muscle weakness, is also noted in some. Other less common manifestations include short stature, heliotrope-like rash on eyelids, severe tylosis on feet and hyperhidrosis of hands and feet. Hepatosplenomegaly is also reported. Lipodystrophy is progressive and irreversible.

Etiology
NNS is due to a mutation in the PSMB8 gene (6p21.3) encoding the beta5i subunit of immunoproteasome. To date, all examined Japanese patients show the same homozygous c.602G>T (Gly201Val) mutation with a founder effect. Immunoproteasome is involved in proteolysis and maintenance of cell homeostasis. If proteolysis is disrupted this can lead to the accumulation of ubiquitinated and oxidized proteins and the hyperactivation of p38 MAPK signaling with cell stress. The p38 MAPK-induced IL-6 overproduction is thought to be responsible, at least in part, for the manifestations seen in this disease.

Diagnostic methods
Diagnosis is based on the presence of at least 5 out of 8 proposed criteria for NNS: an autosomal recessive inheritance pattern, pernio-like purplish lesions (on hands and feet), ''haunting'' nodular erythema, repetitive spiking fever, long clubbed fingers and toes with joint contractures, progressive upper body lipomuscular atrophy/emaciation, hepatosplenomegaly and basal ganglion calcification on computed tomography (CT) scans. Not all of these features are apparent until childhood. Histopathologic examination reveals focal mononuclear cell infiltration with vasculopathy. Laboratory findings include constantly elevated C-reactive protein (CRP) levels and hyper-gamma-globulinemia. Autoantibody titers increase as the disease progresses in some but remain negative in others. Molecular genetic testing can identify a disease causing mutation, confirming diagnosis.

Differential diagnosis
Differential diagnoses include other forms of proteasome disability syndrome, mucopolysaccharidosis, familial partial lipodystrophy, systemic lupus erythematosus, lupus erythematosus panniculitis, dermatomyositis, Sjögren syndrome, inclusion body myositis, Aicardi-Goutières syndrome, Weber-Christian disease and cryopyrin-associated periodic syndrome (see these terms).

Antenatal diagnosis
Prenatal diagnosis is possible but has never been performed.

Genetic counseling
NNS is inherited in an autosomal recessive manner and genetic counseling is possible.

Management and treatment
There is no effective therapeutic regimen for NNS. Fever and skin lesions respond well to systemic steroid administration but usually reoccur after tapering. Also, there are many side effects (growth retardation, glaucoma and central obesity) associated with long-term systemic steroid use. Tocilizumab has shown efficacy in some patients. Although kallidinogenase and dapsone have been reported to be effective in some, the effect is temporary. These treatments are all ineffective in halting lipodystrophy progression.

Prognosis
Although some of the symptoms of NNS can be lessened with treatment, the prognosis remains relatively poor. Some may die from sudden cardiac failure, probably due to lung insufficiency.

Visit the Orphanet disease page for more resources.
Last updated: 3/1/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 59 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the Leydig cells 0010789
Arthralgia
Joint pain
0002829
Arthrogryposis multiplex congenita 0002804
Elevated erythrocyte sedimentation rate
High ESR
0003565
Erythema nodosum 0012219
Hepatomegaly
Enlarged liver
0002240
Hyperostosis
Bone overgrowth
0100774
Joint stiffness
Stiff joint
Stiff joints
[ more ]
0001387
Lipoatrophy
Loss of fat tissue in localized area
0100578
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever
[ more ]
0001954
Skin rash 0000988
Splenomegaly
Increased spleen size
0001744
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin
[ more ]
0001482
30%-79% of people have these symptoms
Clubbing of fingers
Clubbed fingers
Clubbing (hands)
Finger clubbing
[ more ]
0100759
Clubbing of toes 0100760
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased
[ more ]
0000975
Increased circulating antibody level 0010702
Lymphadenopathy
Swollen lymph nodes
0002716
Muscle weakness
Muscular weakness
0001324
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting
[ more ]
0003202
5%-29% of people have these symptoms
Abnormal pyramidal sign 0007256
Arachnodactyly
Long slender fingers
Spider fingers
[ more ]
0001166
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat
[ more ]
0011675
Cardiomegaly
Enlarged heart
Increased heart size
[ more ]
0001640
Congestive heart failure
Cardiac failure
Cardiac failures
Heart failure
[ more ]
0001635
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation
[ more ]
0001256
Macroglossia
Abnormally large tongue
Increased size of tongue
Large tongue
[ more ]
0000158
Macrotia
Large ears
0000400
Microcytic anemia 0001935
Prominent nose
Big nose
Disproportionately large nose
Increased nasal size
Increased size of nose
Large nose
Pronounced nose
[ more ]
0000448
Respiratory insufficiency
Respiratory impairment
0002093
Right bundle branch block 0011712
Seizure 0001250
Short stature
Decreased body height
Small stature
[ more ]
0004322
Thick lower lip vermilion
Increased volume of lower lip
Plump lower lip
Prominent lower lip
[ more ]
0000179
Percent of people who have these symptoms is not available through HPO
Abnormally large globe
Increased size of eyes
Large eyes
[ more ]
0001090
Adipose tissue loss
Loss of fat tissue
0008887
Anemia
Low number of red blood cells or hemoglobin
0001903
Autosomal recessive inheritance 0000007
Basal ganglia calcification 0002135
Bone pain 0002653
Camptodactyly of finger
Permanent flexion of the finger
0100490
Conjunctivitis
Pink eye
0000509
Elbow flexion contracture
Contractures of elbows
Elbow contracture
Elbow contractures
[ more ]
0002987
Elevated hepatic transaminase
High liver enzymes
0002910
Episcleritis
Inflammation of the thin layer on top of the white part of eye
0100534
Erythema 0010783
Failure to thrive
Faltering weight
Weight faltering
[ more ]
0001508
Finger swelling 0025131
Flexion contracture of toe 0005830
Growth abnormality
Abnormal growth
Growth issue
[ more ]
0001507
Hyperpigmentation of the skin
Patchy darkened skin
0000953
Hypertriglyceridemia
Increased plasma triglycerides
Increased serum triglycerides
Increased triglycerides
[ more ]
0002155
Lipodystrophy
Inability to make and keep healthy fat tissue
0009125
Long fingers 0100807
Osteopenia 0000938
Panniculitis
Inflammation of fat tissue
0012490
Stiff skin 0030053
Thrombocytopenia
Low platelet count
0001873
Showing of 59 |
Last updated: 7/1/2020

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Nakajo Nishimura syndrome. This website is maintained by the National Library of Medicine.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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