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Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency


Other Names:
Psychomotor delay due to S-adenosylhomocysteine hydrolase deficiency; Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency; Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase
Categories:
Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency (SAHH deficiency) is a muscle disease associated with high blood levels of methionine and creatine kinase (CK). The main symptoms are psychomotor delay, behavioral disorders, severe myopathy, and delayed myelination from birth. Myelin is the layer covering the axons of nerves and plays an important role in nerve impulse conduction. SAHH deficiency is caused by mutations in the AHCY gene. Inheritance is autosomal recessive.[1][2]  A methionine-restricted diet, together with creatine supplements, may partly improve the delayed myelination and psychomotor development. The outcome depends upon the severity of the disease.[2]
Last updated: 12/5/2016
Very few patients have being reported with this disease.  SAHH patients may not have any symptoms. The observed signs and symptoms in the reported patients included:[1][2]
  • Muscle disease (myopathy) with a blood exam showing an increase of the CK activity (in 100% of the reported cases)
  • Hypotonia
  • Developmental delay
  • Behavioral disorders
  • Very small head (microcephaly)
  • Myelination delay
  • Strabismus
  • Problems with blood coagulation
  • Liver disease
Two sisters had fetal hydrops, brain anomalies and respiratory failure and death in early infancy. Also, a recent report described a 29 year old woman who had liver cancer.[2]
Last updated: 12/5/2016

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.

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Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Elevated hepatic transaminase
High liver enzymes
0002910
Hyperhomocystinemia
Elevated blood homocystine
0002160
Hypoalbuminemia
Low blood albumin
0003073
30%-79% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Cerebellar hypoplasia
Small cerebellum
Underdeveloped cerebellum
[ more ] 		0001321
CNS hypomyelination 0003429
Delayed myelination 0012448
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood
[ more ] 		0002376
Elevated coagulation factor V activity 0011996
Elevated serum creatine kinase
Elevated blood creatine phosphokinase
Elevated circulating creatine phosphokinase
Elevated creatine kinase
Elevated serum CPK
Elevated serum creatine phosphokinase
High serum creatine kinase
Increased CPK
Increased creatine kinase
Increased creatine phosphokinase
Increased serum CK
Increased serum creatine kinase
Increased serum creatine phosphokinase
[ more ] 		0003236
Esotropia
Inward turning cross eyed
0000565
Failure to thrive
Faltering weight
Weight faltering
[ more ] 		0001508
Global developmental delay 0001263
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth
[ more ] 		0001510
Hydrops fetalis 0001789
Hyperintensity of cerebral white matter on MRI 0030890
Hypofibrinogenemia 0011900
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Hypoplasia of the pons 0012110
Infantile muscular hypotonia
Decreased muscle tone in infant
0008947
Muscular dystrophy 0003560
Poor head control 0002421
Prolonged prothrombin time 0008151
Reduced antithrombin III activity 0001976
Reduced factor VII activity 0008169
Short attention span
Poor attention span
Problem paying attention
[ more ] 		0000736
5%-29% of people have these symptoms
Abnormality of hair texture 0010719
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality
[ more ] 		0000164
Cardiomyopathy
Disease of the heart muscle
0001638
Hepatocellular carcinoma 0001402
Hypermethioninemia
Increased methionine in blood
0003235
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Pes planus
Flat feet
Flat foot
[ more ] 		0001763
Respiratory failure 0002878
Sensorimotor neuropathy
Nerve damage causing decreased feeling and movement
0007141
Ventriculomegaly 0002119
Widened subarachnoid space 0012704
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ] 		0001249
Motor delay 0001270
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Last updated: 7/1/2020
Because this disease affects many organs and may begin before birth, it may be difficult to treat. It is possible that blood abnormalities are present in all patients in utero.[1]

Treatment may include:[2]
  • A low methionine diet: This can decrease and sometimes even normalize the abnormalities in the blood exams. Patients have to be on a protein restricted diet and supplemented with a methionine-free amino acid mixture.
  • Supplementation with phosphatidylcholine and creatine: At this time there is no evidence that this treatment is effective.
  • Liver transplantation: Recently, liver transplantation was successfully done in one girl at the age of 40 months, but longer follow-up is needed to know the outcome of the liver transplantation.
The treatment outcome depends on the severity of the disease. It is not known whether even early intervention could help in severe cases. In others, it is possible that earlier initiation of treatment may improve the outcome. Regular careful evaluation of all body systems is indicated, mainly of the nervous system, psychomotor development, muscles, liver and blood (for coagulation). This includes imaging studies, especially regular liver imaging and blood exams.[2]
Last updated: 12/5/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

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.

In-Depth Information

  • 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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  1. Hypermethioninemia. Genetics Home Reference:. April, 2007; https://ghr.nlm.nih.gov/condition/hypermethioninemia.
  2. Baric I. Consensus recommendations for the diagnosis, treatment and follow-up of inherited methylation disorders. J Inherit Metab Dis. September 26, 2016; https://www.ncbi.nlm.nih.gov/pubmed/27671891.