2 CASE REPORT
2.1 Case history and examination
A 5-year-old girl, born of a non-consanguineous marriage, presented with
clinical indications of low to moderate-grade fever persisting for the
past 2 years, along with recurrent skin lesions and infections. The
patient, a first-born child of non-consanguineous parents (G1P1L1), had
a birth weight of 3800 grams and current weight of 17 kg. Her date of
birth was January 30, 2017, and she had a history of normal
neurodevelopment. She was a native of Tajikistan with no known history
of specific diseases. There were no positive points in the family
history regarding similar conditions.
Approximately 2 years ago, the patient started experiencing episodes of
low to moderate-grade fever and recurrent generalized skin lesions,
affecting the trunk, abdomen, and face. The skin lesions exhibited a
recurrent pattern. She also complained of arthralgia. Initially,
multiple physicians in Tajikistan suspected a dermatological condition.
However, due to the lack of improvement in the patient’s symptoms, she
was referred to BLK-MAX Hospital in central Delhi in January 2023, with
a history of fever persisting for a year and the recent development of
pustular skin lesions over the past month. At BLK-MAX Hospital, primary
immunodeficiency was suspected, and further tests were requested. In
August 2023, the patient was referred to the rheumatology clinic of
Mofid Children’s Hospital in Tehran, Iran.
During the evaluation in the rheumatology clinic, the patient’s height
and weight were measured at 100 cm and 17 kg, respectively. Physical
examination revealed pallor, moderate-grade fever with a sporadic
pattern, and no skin lesions at the time of admission. There were no
signs of icterus, lymphadenopathy, organomegaly, and the chest
examination was clear. The patient had a history of arthritis,
arthralgia, and sore throat in the course of the disease. Immunology
consultation was conducted, and an immunological examination, including
complete blood count (CBC), CD markers, and immunoglobulin levels, was
performed. The hematological, biochemical and immunological findings of
the patient are provided in (Table 1).
Whole-exome sequencing (WES) was performed on a blood sample from the
patient. Variant interpretation of specific variants of interest was
conducted following the guidelines of the American College of Medical
Genetics and Genomics (ACMG). A heterozygous missense variation was
identified in exon 4 of the MVK gene, resulting in the amino acid
substitution of asparagine for aspartic acid at codon 100
(C.298G>A; P. Asp100Asn). This variant is classified as
having uncertain significance according to the ACMG guidelines and is
associated with the OMIM phenotype of Hyper IgD Syndrome, which is
typically caused by homozygous or compound heterozygous mutations in the
MVK gene (Table 2 ). The clinical symptoms of the patient are
consistent with this phenotype. The skin manifestation of the patient is
showed in (Figure1).
We should mention; in our case, we observed significantly elevated
levels of mevalonic acid in the patient’s urine, indicating a
substantial accumulation of mevalonate due to mevalonate kinase
deficiency.
2.2 Treatment, outcome, and follow-up
Based on the patient’s clinical symptoms and genetic findings, a
diagnosis of Hyper-IgD syndrome with periodic fever (HIDS) was made. Due
to the severity of the symptoms, medications such as methylprednisolone
pulse (IV) at a dosage of 30 mg/kg/day for three doses, followed by oral
prednisolone, were deemed necessary. In order to address the patient’s
symptoms, treatment with Anakinra was initiated. Notably, this resulted
in a remarkable improvement in both the patient’s symptoms and
laboratory investigations.