Systemic Lupus Erythematosus with Prolidase Deficiency in a 16 Year Old Boy

Introduction: Prolidase deficiency (PD) is a rare autosomal recessive disorder which may have a wide spectrum of clinical features. The disorder is caused by a mutation in the PEPD gene.

Objective: PD is considered to be monogenic cause that are suspected in onset of SLE.

Methods: Two siblings had cognitive impairment, rash or skin ulceration, hyper IgG-emia, hyper IgE-emia. Younger sister had severe interstitial pneumonia. They were diagnosed as PD by performed whole-exome sequencing and measurement of prolidase enzyme activity.

Case1: At the age of 16 years, older brother had gross hematuria. Laboratory findings included hemoglobin (10.6 gm/dl), white blood cell (2,500/μl), platelet (87 × 10³/μl), elevated erythrocyte sedimentation rate (ESR). Immunologic evaluation revealed high immunoglobulins: IgG 4,015 mg/dl, IgA 662 mg/dl, IgM 87 mg/dl, and very high IgE 18,563 IU/ml. Antinuclear antibodies (ANA) were positive in a titer of 1:80 (homogenous pattern). Antibodies to double-stranded DNA IgG and SS-A were positive. Complement C₃, C₄, were low. He underwent a kidney biopsy which confirmed the LN diagnosis with class IV-G (A/C) with mesangial diffuse proliferative changes, with crescent.

He was started on Intravenous pulses of methylprednisolone and MMF. Later, four infusions of rituximab were given due to incomplete response. He is currently stable in complete remission. His levels of anti-dsDNA and C3 normalised.

Case2: A younger sister was diagnosed as interstitial pneumonia at six months old. She had recurrent pyoderma, clubbing. ANA and SS-A were positive. Antibodies to DNA IgG was negative. Complement were low. Her urinary tests showed normal. She has been treated with low dose of prednisolone and cyclosporine A for interstitial pneumonia.

Conclusion: PD was diagnosed in siblings with skin lesions, cognitive impairment, hyper IgG-emia, hyper IgE-emia. And they have ANA and low levels of complement. PD might be a risk factor for the development of SLE.