Clin Case Rep. 2025 Sep;13(9): e70847
Congenital disorders of glycosylation (CDG) are a heterogeneous group of inherited metabolic diseases (IMD) characterized by defects in the synthesis and modification of glycoproteins and glycolipids. One of these disorders is ATP6AP1-CDG, a rare X-linked disease with approximately 30 cases reported so far. Symptoms associated with ATP6AP1-CDG include immunodeficiency, liver dysfunction, and neurological manifestations. This report presents the first case of ATP6AP1-CDG in Iran and the Middle East, in a 5-month-old male infant presenting with fever, vomiting, diarrhea, and poor feeding. The patient had a history of similar symptoms at three and 4 months and had been hospitalized with a diagnosis of gastrointestinal (GI) infection. In addition, he had a history of recurrent seizures, which first began at 45 days old, and was treated with phenobarbital. On physical examinations, the patient was lethargic, severely hypotonic with decreased primitive reflexes, and dehydrated with dry mucous membranes and white plaques of candidiasis. There was no tenderness, guarding, or hepatosplenomegaly in the abdominal examination. Laboratory blood tests were requested, which revealed leukocytosis and normal liver and kidney functions, with negative blood, urine, cerebrospinal fluid, and stool cultures for bacterial growth. Considering the history of recurrent infections, idiopathic seizures, suspected immunodeficiency in the patient's deceased sibling and parental consanguinity, primary immunodeficiency was suspected as a possible diagnosis for the patient. Therefore, a panel of immune function tests was requested, all of which were within the normal range. This panel consisted of IgM, IgG, IgA, B-Cell markers (CD19), T-Cell markers (CD3, CD4, and CD8), TRECs, NK-Cell markers (CD16 and CD56), LTT-PHA, LTT-BCG, and CH50. Furthermore, whole exome sequencing (WES) was requested, which revealed a novel hemizygous deletion in the ATP6AP1 gene (NM_001183.6), designated as c.111_116del; p.Ala40_Ala41del (chrX:153657133 TGGCGGC>T, hg19 assembly).
Keywords: ATP6AP1; Ac45 protein; case report; congenital disorders of glycosylation; immunological deficiency syndromes; inborn errors of metabolism