Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency

Alternate names

Psychomotor delay due to S-adenosylhomocysteine hydrolase deficiency; Psychomotor retardation due to S-adenosylhomocysteine hydrolase deficiency; Hypermethioninemia with deficiency of S-adenosylhomocysteine hydrolase

Definition

Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency (SAHH deficiency) is a muscle disease associated with high blood levels of methionine and creatine kinase (CK).

Cause

SAHH deficiency is caused by mutations in the AHCY gene.

Inheritance

Autosomal recessive inheritance, a 25% chance

Inheritance is autosomal recessive.

Signs and symptoms

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:

• 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.

Diagnosis

Molecular Genetics Tests may include:

• Deletion/duplication analysis
• Sequence analysis of the entire coding region
• Targeted variant analysis
• Sequence analysis of select exons

Treatment

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. Treatment may include: 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.

NIH genetic and rare disease info

• NIH info on Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency

Hypermethioninemia due to S-adenosylhomocysteine hydrolase deficiency is a rare disease.